A genetic variant in kidney donors is linked to an increased likelihood that the graft will fail, researchers said.

Action Points

Explain that this study found that a genetic variant seen in some donors is associated with an increased risk of failure of a kidney transplant.

Explain that the gene involved, CAV1, makes a protein that is involved in tissue fibrosis as well as vascular proliferation.

A genetic variant in kidney donors is linked to an increased likelihood that the graft will fail, researchers said.

The variation is in the gene for CAV1, a protein that is involved in tissue fibrosis as well as vascular proliferation, according to Richard Borrows, MB, of Queen Elizabeth Hospital in Birmingham, England, and colleagues.

While only a minority of kidney donors have the genetic variation, it "shows potential" as a method of identifying which transplants have a greater risk of failure, Borrows and colleagues said in the April 7 issue of the Journal of the American Medical Association.

Study of the variant may also help to expand the scientific understanding of how renal fibrosis arises, they said.

The researchers looked for common variations in CAV1 among 785 white kidney transplant donors and their respective recipients in Birmingham, England, between 1996 and 2006, using a single nucleotide polymorphism (SNP) approach.

Of the SNPs they tested, only one -- dubbed rs4730751 -- was associated with an increased risk of allograft failure.

The variation in question is an adenine for cytosine switch, and kidneys from donors with the AA genotype were significantly more likely to fail the transplant, compared with those from donors with a non-AA genotype, the researchers found.

Specifically, in an adjusted Cox regression model, the hazard ratio for failure with AA- versus non-AA genotypes was 1.97, with a 95% confidence interval from 1.29 to 3.16, which was significant at P=0.002, they reported in the journal.

Overall, the graft failure rate for donor kidneys with the AA genotype was 38.6%, compared with 22.3% for donor genotype CC, and 22.2% for donor genotype AC, Borrows and colleagues said.

To validate the finding, the researchers looked at a genotypes from an independent cohort of 697 kidney donors in Belfast, Northern Ireland, between 1986 and 2005.

In that cohort, they found:

In an adjusted Cox model, the hazard ratio for failure with an AA-genotype was 1.56 (with a 95% confidence interval from 1.07 to 2.27), compared with non-AA genotypes. The risk was significant at P=0.02.

In each cohort, the researchers found, fewer than 10% of donors had the AA genotype.

In the Birmingham cohort, the researchers said, histological assessment was performed in 155 of the 184 grafts that failed, revealing that predominant interstitial fibrosis was increased in recipients of genotype AA kidneys.

Specifically, the condition was found in 59% of those whose genotype AA kidney failed, compared with 26% of those whose non-AA kidney failed. The difference was significant at P=0.003, and other causes of graft failure were similar between donor genotypes.

The researchers did not report an analysis of graft failure causes for the Belfast cohort.

The implication of the findings, they said, is that the SNP rs4730751 (or one that is inherited along with it) promotes tissue fibrosis, leading to the failure of the kidney grafts. There was no evidence that the effect was caused either by acute rejection or delayed graft function.

The study was supported by the University Hospital Birmingham Charities. The researchers made no financial disclosures.